title: Assessment of effects of chronic hydrogen sulfide poisoning on cytochrome P450 isoforms activity of rats by cocktail approach.
abstract: Hydrogen sulfide (H₂S) is one of the neurotoxic gases with suffocating and irritating. Its main target organs of toxic effects are the central nervous system and respiratory system. Cocktail method was used to evaluate the influence of chronic hydrogen sulfide poisoning on the activities of cytochrome P450 (CYP450) isoforms CYP1A2, CYP2C9, CYP2B6 and CYP2D6, which were reflected by the changes of pharmacokinetic parameters of 4 specific probe drugs phenacetin, tolbutamide bupropion and metroprolol, respectively. The experimental rats were randomly divided into two groups, control group and chronic hydrogen sulfide poisoning group. The chronic hydrogen sulfide poisoning group rats were inhaled 20 ppm for 1 h twice a day for 40 d. The mixture of 4 probes was given to rats through sublingual veins and the blood samples were obtained at a series of time-points through the caudal vein. The concentrations of probe drugs in rat plasma were measured by liquid chromatography-mass spectrometry (LC-MS). In the experiment for chronic hydrogen sulfide poisoning and control group, there was a statistically significant difference in the area under the plasma concentration-time curve from zero to infinity (AUC(0-∞)), plasma clearance (CL) and maximum plasma concentration (C(max)) for phenacetin and bupropion, while there was no statistical pharmacokinetics difference for tolbutamide and metoprolol. Chronic hydrogen sulfide poisoning could induce the activity of CYP1A2 and CYP2B6 of rats.
authors.affiliation: Analytical and Testing Center of Wenzhou Medical University.
authors.forename: Xianqin
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaole
authors.initials: X
authors.lastname: Chen
authors.forename: Mengchun
authors.initials: M
authors.lastname: Chen
authors.forename: Guoxin
authors.initials: G
authors.lastname: Hu
authors.forename: Jianshe
authors.initials: J
authors.lastname: Ma
authors.forename: Jianchun
authors.initials: J
authors.lastname: Pan
authors.forename: Lufeng
authors.initials: L
authors.lastname: Hu
authors.forename: Guanyang
authors.initials: G
authors.lastname: Lin
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D016642:Bupropion / Q000097:blood; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D065702:Cytochrome P-450 CYP2B6; D006862:Hydrogen Sulfide / Q000009:adverse effects*; D008297:Male; D010615:Phenacetin / Q000097:blood; D020033:Protein Isoforms; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014044:Tolbutamide / Q000097:blood
chemical_list: D020033:Protein Isoforms; D016642:Bupropion; D014044:Tolbutamide; D001189:Aryl Hydrocarbon Hydroxylases; D019388:Cytochrome P-450 CYP1A2; D065702:Cytochrome P-450 CYP2B6; D010615:Phenacetin; D006862:Hydrogen Sulfide